Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis
Ali Al Ahmari1,5, Osama Alsmadi2,6, Atia Sheereen2, Tanziel Elamin2, Amal Jabr2, Lina El-Baik2, Safa Alhissi2, Bandar Al Saud3, Moheeb Al-Awwami4, Ibrahim Al Fawaz1,5, Mouhab Ayas1,5, Khawar Siddiqui1, Abbas Hawwari2,7
1Department of Pediatric Hematology/Oncology, 2Section of Immunogenetics, Department of Genetics, Research Center, 3Department of Pediatric Allergy/Immunology, 4Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, 5College of Medicine, AlFaisal University, Riyadh, Saudi Arabia, 6Cell Therapy, Applied Genomics, King Hussein Cancer Center, Amman, Jordan, 7King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City Hospital, Al-Ahsa, Saudi Arabia
Correspondence to: Ali Al-Ahmari, M.D.
Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia
Published online: June 4, 2021.
© The Korean Journal of Hematology. All rights reserved.

Background: Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients.
Methods: FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed.
Results: Homozygous mutations and mono-allelic variants were identified in 66 (75.9%) and 3 (3.5%) of the study participants, respectively. STXBP2 was the most frequently mutated gene (36% of patients) and mutations in STXBP2 and STX11 accounted for 58% of all FHL cases and demonstrated a specific geographical pattern. Patients in the FHL group presented at a significantly younger age than those belonging to the unknown-genetics group (median, 3.9 vs. 9.4 mo; P=0.005). The presenting clinical features were similar among the various genetic groups and the 5-year overall survival (OS) was 55.4% with a 5.6 year median follow-up. Patients with PRF1 mutations had a significantly poorer 5-year OS (21.4%, P=0.008) and patients undergoing hematopoietic stem cell transplant (72.4%) had a significantly better 5-year OS (66.5% vs. 0%, P=0.001).
Conclusion: Our study revealed the predominance of the STXBP2 mutations in Saudi patients with FHL. A genetic diagnosis was possible in 80% of the cohort and our data showed improved survival in FHL patients who underwent hematopoietic stem cell transplant.
Keywords: Hemophagocytic lympho-histiocytosis, Genetic mutation, PRF1, UNC13D, STX11, STXBP2


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